Abstract
Children with Down syndrome (DS) show a spectrum of clinical anomalies, including cognitive impairment, cardiac malformations, and craniofacial dysmorphy. Moreover, hematologists have also noted that these children commonly show macrocytosis, abnormal platelet counts, and an increased incidence of transient myeloproliferative disease (TMD), acute megakaryocytic leukemia (AMKL), and acute lymphoid leukemia (ALL). In this review, we summarize the clinical manifestations and characteristics of these leukemias, provide an update on therapeutic strategies and patient outcomes, and discuss the most recent advances in DS-leukemia research. With the increased knowledge of the way in which trisomy 21 affects hematopoiesis and the specific genetic mutations that are found in DS-associated leukemias, we are well on our way toward designing improved strategies for treating both myeloid and lymphoid malignancies in this high-risk population.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Transformation, Neoplastic / genetics*
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Chromosomes, Human, Pair 21 / genetics
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Disease Models, Animal
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Disease Progression
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Down Syndrome / blood
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Down Syndrome / complications*
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Down Syndrome / genetics
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GATA1 Transcription Factor / genetics
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Gene Expression Regulation, Leukemic
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Genetic Predisposition to Disease
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Hematopoiesis, Extramedullary / genetics
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Humans
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Incidence
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Janus Kinases / genetics
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Leukemia, Megakaryoblastic, Acute / drug therapy
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Leukemia, Megakaryoblastic, Acute / epidemiology
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Leukemia, Megakaryoblastic, Acute / etiology*
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Leukemia, Megakaryoblastic, Acute / genetics
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Liver / embryology
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Liver / pathology
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Mice
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MicroRNAs / genetics
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Mutation
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Myeloproliferative Disorders / congenital*
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Myeloproliferative Disorders / drug therapy
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Myeloproliferative Disorders / epidemiology
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Myeloproliferative Disorders / etiology
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Myeloproliferative Disorders / genetics
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Neoplasm Proteins / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Preleukemia / congenital*
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Preleukemia / drug therapy
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Preleukemia / epidemiology
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Preleukemia / etiology
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Preleukemia / genetics
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RNA, Neoplasm / genetics
Substances
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GATA1 Transcription Factor
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GATA1 protein, human
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MicroRNAs
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Neoplasm Proteins
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RNA, Neoplasm
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Janus Kinases